Replication and functional genomic analyses of the breast cancer susceptibility locus at 6q25.1 generalize its importance in women of chinese, Japanese, and European ancestry.

Abstract

We evaluated the generalizability of a single nucleotide polymorphism (SNP), rs2046210 (A/G allele), associated with breast cancer risk that was initially identified at 6q25.1 in a genome-wide association study conducted among Chinese women. In a pooled analysis of more than 31,000 women of East-Asian, European, and African ancestry, we found a positive association for rs2046210 and breast cancer risk in Chinese women [ORs (95% CI) = 1.30 (1.22-1.38) and 1.64 (1.50-1.80) for the AG and AA genotypes, respectively, P for trend = 1.54 × 10⁻³⁰], Japanese women [ORs (95% CI) = 1.31 (1.13-1.52) and 1.37 (1.06-1.76), P for trend = 2.51 × 10⁻⁴], and European-ancestry American women [ORs (95% CI) = 1.07 (0.99-1.16) and 1.18 (1.04-1.34), P for trend = 0.0069]. No association with this SNP, however, was observed in African American women [ORs (95% CI) = 0.81 (0.63-1.06) and 0.85 (0.65-1.11) for the AG and AA genotypes, respectively, P for trend = 0.4027]. In vitro functional genomic studies identified a putative functional variant, rs6913578. This SNP is 1,440 bp downstream of rs2046210 and is in high linkage disequilibrium with rs2046210 in Chinese (r(2) = 0.91) and European-ancestry (r² = 0.83) populations, but not in Africans (r² = 0.57). SNP rs6913578 was found to be associated with breast cancer risk in Chinese and European-ancestry American women. After adjusting for rs2046210, the association of rs6913578 with breast cancer risk in African Americans approached borderline significance. Results from this large consortium study confirmed the association of rs2046210 with breast cancer risk among women of Chinese, Japanese, and European ancestry. This association may be explained in part by a putatively functional variant (rs6913578) identified in the region.

• Authors: Qiuyin Cai, Wanqing Wen, Shimian Qu, Guoliang Li, Kathleen M Egan, Kexin Chen, Sandra L Deming, Hongbing Shen, Chen-Yang Shen, Marilie D Gammon, William J Blot, Keitaro Matsuo, Christopher A Haiman, Ui Soon Khoo, Motoki Iwasaki, Regina M Santella, Lina Zhang, Alecia Malin Fair, Zhibin Hu, Pei-Ei Wu, Lisa B Signorello, Linda Titus-Ernstoff, Kazuo Tajima, Brian E Henderson, Kelvin Y K Chan, Yoshio Kasuga, Polly A Newcomb, Hong Zheng, Yong Cui, Furu Wang, Ya-Lan Shieh, Hiroji Iwata, Loic Le Marchand, Sum Yin Chan, Martha J Shrubsole, Amy Trentham-Dietz, Shoichiro Tsugane, Montserrat Garcia-Closas, Jirong Long, Chun Li, Jiajun Shi, Bo Huang, Yong-Bing Xiang, Yu-Tang Gao, Wei Lu, Xiao-Ou Shu, Wei Zheng
• Journal: Cancer research (Cancer Res) Vol. 71 Issue 4 Pg. 1344-55 (Feb 15 2011) ISSN: 1538-7445 [Electronic] United States
• PMID: 21303983 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Validation Study)
• Copyright: ©2011 AACR.

Topics

• Asian People (genetics)
• Breast Neoplasms (epidemiology, ethnology, genetics)
• Carcinoma (epidemiology, ethnology, genetics)
• Case-Control Studies
• Chromosomes, Human, Pair 6 (genetics)
• Female
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Genomics (methods)
• Genotype
• Humans
• Middle Aged
• Polymorphism, Single Nucleotide
• White People (genetics)